{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:53:55Z","timestamp":1792785235183,"version":"4.5.0"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"The National Key Research and Development Program of China","award":["2023YFD1400200"],"award-info":[{"award-number":["2023YFD1400200"]}]},{"name":"National Natural Science Foundation of China","award":["32470201"],"award-info":[{"award-number":["32470201"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["32370208"],"award-info":[{"award-number":["32370208"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:p>\n                    Autophagy degrades and recycles intracellular material, allowing cells to maintain homeostasis and adapt to environmental stress. In the rice blast fungus\n                    <jats:italic toggle=\"yes\">Magnaporthe oryzae<\/jats:italic>\n                    , the core autophagy protein MoAtg8 is required for autophagosome formation and host infection. Here, we determined the crystal structure of MoAtg8 and used it for structure-guided virtual screening of a focused compound library enriched for natural products and autophagy-related molecules. This screen identified nordihydroguaiaretic acid (NDGA), a naturally occurring lignan, as a MoAtg8-binding compound. NDGA suppressed conidial germination and appressorium formation, disrupted membrane integrity, and reduced pathogenicity in\n                    <jats:italic toggle=\"yes\">M. oryzae<\/jats:italic>\n                    , with no detectable phytotoxicity to rice under the conditions tested. Mechanistically, the 5-lipoxygenase Mo5Lox, a target of NDGA, bound NDGA with lower affinity than MoAtg8. MoAtg8 associated with NDGA through Gln81 and promoted its autophagy-dependent delivery to vacuoles, thereby reducing compound availability to toxicity-associated targets. Disruption of autophagy or mutation of Gln81 in MoAtg8 increased fungal sensitivity to NDGA. These findings identify an autophagy-mediated detoxification route for an exogenous antifungal compound and reveal how MoAtg8-dependent trafficking modulates NDGA efficacy in a plant-pathogenic fungus.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2623430123","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:37:33Z","timestamp":1792085853000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Structure-based targeting of Atg8 uncovers its essential role in autophagy-mediated detoxification"],"prefix":"10.1073","volume":"123","author":[{"given":"Jiongyi","family":"Yan","sequence":"first","affiliation":[{"name":"State Key Laboratory for Quality and Safety of Agro-products, Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Biotechnology, Zhejiang University","place":["Hangzhou, 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Y. Yan X. M. Zhu Data from \u201cAutophagy\u2011related proteins of Magnaporthe oryzae\u2011MoAtg8.\u201d RCSB PDB. https:\/\/doi.org\/10.2210\/pdb9J5G\/pdb. Deposited 12 August 2024.","DOI":"10.2210\/pdb9j5g\/pdb"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.021"},{"key":"e_1_3_4_24_2","unstructured":"X. Zhu Data from \u201cCompound-library source metadata and structure-informed filtering summary.\u201d Figshare. https:\/\/doi.org\/10.6084\/m9.figshare.33941869. Deposited 19 September 2026."},{"key":"e_1_3_4_25_2","article-title":"Measuring cell death by propidium iodide uptake and flow cytometry","volume":"2016","author":"Crowley L. C.","year":"2016","unstructured":"L. C. Crowley , Measuring cell death by propidium iodide uptake and flow cytometry. Cold Spring Harb. Protoc. 2016 (2016).","journal-title":"Cold Spring Harb. 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